Dendritic Cells Augment Choroidal Neovascularization

• Published in: Investigative ophthalmology & visual science 2008-08, Vol.49 (8), p.3666-3670
• Main Authors: Nakai, Kei, Fainaru, Ofer, Bazinet, Lauren, Pakneshan, Pouya, Benny, Ofra, Pravda, Elke, Folkman, Judah, D'Amato, Robert J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; CD11c Antigen - metabolism; Cell Movement; Cell Transplantation; Cells, Cultured; Choroid - blood supply; Choroidal Neovascularization - etiology; Choroidal Neovascularization - metabolism; Dendritic Cells - physiology; Dendritic Cells - transplantation; Disease Models, Animal; Endothelium, Vascular - metabolism; Eye and associated structures. Visual pathways and centers. Vision; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Histocompatibility Antigens Class II - metabolism; Laser Coagulation; Medical sciences; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Ophthalmology; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.07-1640

Dendritic cells (DCs) are innate immune cells that have recently been shown to support angiogenesis in tumors, endometriosis, and lymph nodes. A major cause of legal blindness is wet age-related macular degeneration (wet ARMD), wherein abnormal blood vessels grow under the retina, an abnormality also referred to as choroidal neovascularization (CNV). The purpose of the present study was to investigate the role of DCs in the development of CNV. Laser photocoagulation was used to induce CNV in C57BL/6J mice. The authors analyzed CNV lesions for the presence of DCs using flow cytometry and immunostaining at designated times. They also analyzed the effects of intravenous DC transplantation on CNV development by measuring the lesion area using confocal microscopy 1 week after laser injury. The authors analyzed CNV lesions for the presence of DCs by flow cytometry and observed that CD11c(+) major histocompatibility complex (MHC) class II(+) DCs transiently infiltrated the CNV lesions, reaching a peak at 2 to 4 days after laser injury. These DCs were mostly immature (CD11c(+) MHCII(low)) and expressed vascular endothelial growth factor receptor 2. Immunostaining of laser-induced CNV lesions confirmed that DCs are located at the sites of newly formed blood vessels. Intravenously injected DCs incorporated into the CNV lesions. However, only immature DCs enhanced CNV size. These results suggest a role for DCs in promoting angiogenesis and lesion growth in laser-induced CNV. The present data suggest that DCs may represent potential cellular targets for therapeutic intervention in wet ARMD.